Glutamate prevents altered mitochondrial function following recurrent low glucose in hypothalamic but not cortical primary rat astrocytes.
dc.contributor.author | Weightman Potter, PG | |
dc.contributor.author | Ellacott, KLJ | |
dc.contributor.author | Randall, AD | |
dc.contributor.author | Beall, C | |
dc.date.accessioned | 2023-01-25T09:03:22Z | |
dc.date.issued | 2022-10-29 | |
dc.date.updated | 2023-01-24T20:05:22Z | |
dc.description.abstract | Astrocytes contribute to glutamatergic signalling, which is required for hypoglycaemia counterregulation and is impaired by recurrent insulin-induced hypoglycaemia. This study examined the glutamate response of astrocytes when challenged with acute and recurrent low glucose (RLG) exposure. The metabolic responses of cortical (CRTAS) and hypothalamic (HTAS) primary rat astrocytes were measured in acute and recurrent low glucose using extracellular flux analyses. RLG caused mitochondrial adaptations in both HTAS and CRTAS, many of which were attenuated by glutamate exposure during low glucose (LG) treatments. We observed an increase in capacity of HTAS to metabolise glutamine after RLG exposure. Demonstrating astrocytic heterogeneity in the response to LG, CRTAS increased cellular acidification, a marker of glycolysis in LG, whereas this decreased in HTAS. The directional change in intracellular Ca2+ levels of each cell type, correlated with the change in extracellular acidification rate (ECAR) during LG. Further examination of glutamate-induced Ca2+ responses in low glucose treated CRTAS and HTAS identified sub-populations of glucose-excited- and glucose-inhibited-like cells with differing responses to glutamate. Lastly, release of the gliotransmitter ATP by HTAS was elevated by RLG, both with and without concurrent glutamate exposure. Therefore, hypothalamic astrocytes adapt to RLG by increasing glutamate uptake and oxidation in a manner that prevents RLG-induced mitochondrial adaptations. | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | Juvenile Diabetes Research Foundation | en_GB |
dc.description.sponsorship | European Federation for the Study of Diabetes | en_GB |
dc.description.sponsorship | Novo Nordisk Research Foundation | en_GB |
dc.format.extent | 3422- | |
dc.format.medium | Electronic | |
dc.identifier.citation | Vol. 11, No. 21, article 3422 | en_GB |
dc.identifier.doi | https://doi.org/10.3390/cells11213422 | |
dc.identifier.grantnumber | 13/0004647 | en_GB |
dc.identifier.grantnumber | 3-PDF-2020-941-A-N | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/132321 | |
dc.identifier | ORCID: 0000-0002-4263-0866 (Beall, Craig) | |
dc.identifier | ScopusID: 36175475800 (Beall, Craig) | |
dc.language.iso | en | en_GB |
dc.publisher | MDPI | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/36359822 | en_GB |
dc.rights | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). | en_GB |
dc.subject | astrocytes | en_GB |
dc.subject | diabetes mellitus | en_GB |
dc.subject | glutamic acid | en_GB |
dc.subject | glycemic control | en_GB |
dc.subject | hypoglycemia | en_GB |
dc.subject | hypothalamus | en_GB |
dc.subject | mitochondria | en_GB |
dc.subject | type 1 | en_GB |
dc.title | Glutamate prevents altered mitochondrial function following recurrent low glucose in hypothalamic but not cortical primary rat astrocytes. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-01-25T09:03:22Z | |
dc.identifier.issn | 2073-4409 | |
exeter.article-number | ARTN 3422 | |
exeter.place-of-publication | Switzerland | |
dc.description | This is the final version. Available from MDPI via the DOI in this record. | en_GB |
dc.description | Data Availability Statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. | en_GB |
dc.identifier.journal | Cells | en_GB |
dc.relation.ispartof | Cells, 11(21) | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2022-10-26 | |
dc.rights.license | CC BY | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2022-10-29 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-01-25T09:00:17Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2023-01-25T09:03:26Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2022-10-29 |
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